The COVID-19 pandemic is known to cause disproportionately high mortality in older adults and those with underlying health conditions. A new study published on the preprint server medRxiv* in June 2020 reports that obesity is a risk factor of composite poor outcome of COVID-19 disease. On the other hand, COVID-19 patients with 'composite poor outcome' have higher BMI. Therefore, BMI should be assessed in the management of COVID-19 patients, and special attention should be given to patients with obesity.
COVID-19 pneumonia is associated with high morbidity and mortality, with a high percentage of poor outcomes such as those listed in the study below, and in addition, acute renal injury, shock, and acute cardiac injury. Researchers have been trying to define the risk factors that are associated with a poor prognosis.
The Study: Relating BMI to Outcome
The researchers searched all the available literature from two large databases, including research on obesity and poor COVID-19 outcomes, to define composite poor outcome as mortality, morbidity, intensive care unit (ICU) admission, mechanical ventilation, acute respiratory distress syndrome (ARDS), and severe COVID-19.
One such factor is obesity, which causes dysregulation of the immune response. Obesity also affects normal lung function, due to the fat deposits in the subcutaneous tissue that alter the mechanics of the rib cage as well as the lungs, reducing their compliance. Earlier studies have also shown that the presence of excessive fatty tissue is linked to the increased production of inflammatory cells, as well as a hyper-responsive airway.
ARDS is associated with increased work of breathing, to supply adequate oxygen to the body. When the patient is obese, the work of breathing is made more difficult, which may account for the worse outcome in these patients.
BMI is classified into six groups, from underweight through normal, pre-obesity, through three classes of obesity, from the definition of 30 kg/m2 to over 40 kg/m2. Both Europe and the US are among the regions with the highest prevalence of obesity, but this is a condition that may also be considered a pandemic, as almost a third of the world’s population is overweight or obese.
Study: Association of BMI and Obesity with Composite poor outcome in COVID-19 adult patients: A Systematic Review and Meta-Analysis. Image Credit: Olivier Le Moal / Shutterstock
BMI and Composite Outcome
The meta-analysis using BMI as a continuous outcome showed that a higher BMI was linked to a poor composite outcome. The mean BMI difference was 0.55 kg/m2. With BMI as a dichotomous outcome, the meta-analysis showed that the odds ratio was almost 1.9 for a composite poor outcome with higher BMI.
Earlier studies showed that almost one-third of hospitalized patients or fatalities in the H1N1 pandemic of 2009 were obese, making this an independent risk factor for poor outcomes of H1N1. This is reflected in the current relationship of obesity with a poor outcome of COVID-19 as well.
Though the relationship between the higher BMI and composite poor outcome was weaker with increasing age, the presence of hypertension and type 2 diabetes mellitus did not affect the composite poor outcome.
Mechanical Effects of Obesity
Obesity worsens the impact of lower respiratory tract infections because the mechanical effect of the increased mass of fat in the tissues can reduce airway caliber and increase airway resistance. It also closes the airway and promotes airway hyper-responsiveness as a result of increased inflammation. Thus, a patient with a chest infection who is obese is already at a higher risk of developing worse respiratory symptoms, and of requiring ICU admission or mechanical ventilation.
COVID-19 is no exception, as it has been found to lead to airway closure, ARDS, and respiratory failure. The mechanical effects described above result in weakening of the respiratory muscle and threefold higher oxygen demand. This increased use of oxygen can precipitate respiratory failure and trigger the requirement for supplemental oxygen and even ventilator use. The latter also involves more difficult mask ventilation when the patient is obese.
Adipokines and the Immune Response
Obesity is also associated with a poorer prognosis because of the negative immunoregulation induced by adipose tissue chemokines. The fat cells take part in a host of metabolic and other body processes and serve as a source or harbor for T cells and macrophages, belonging to the adaptive and innate immune system, respectively. When there is too much fat in the body, T cell and macrophage function are impaired, leading to a weak antiviral response.
Simultaneously, obesity is linked with prolonged activation of the innate immune system, with the release of adipokines (signaling molecules released by fat cells) that are not found in lean individuals.
Systemic hyperinflammation in Obese COVID-19 Patients
Adipokine patterns are persistently altered in obese people, and also inflammatory mediators formed from them, like tumor necrosis factor-alpha (TNF-α), interleukin (IL-) 8, and IL-6, high-sensitivity C-reactive protein (hs-CRP) and monocyte chemoattractant protein-1 (MCP-1).
Some studies have shown that an excessive and unregulated release of cytokines, the so-called cytokine storm, worsens the outcome in COVID-19 by directly causing tissue injury and multi-organ dysfunction. The researchers assume that obese COVID-19 patients are likely to develop this type of systemic hyperinflammation in tissues other than the lungs.
Without specific antivirals, the only option for minimizing the toll of COVID-19 is by the use of non-pharmacological interventions to prevent viral spread, while simultaneously addressing lifestyle issues like obesity that also worsen the risk of a poor outcome. The researchers sum up: “Stakeholders have an obligation to encourage the community to implement a healthy lifestyle to reduce the prevalence of overweight and obesity, especially during COVID-19 pandemic.”
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.